IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8 + T Cells

Christopher A. Klebanoff, Steven E. Finkelstein, Deborah R. Surman, Michael K. Lichtman, Luca Gattinoni, Marc R. Theoret, Navrose Grewal, Paul J. Spiess, Paul A. Antony, Douglas C. Palmer, Yutaka Tagaya, Steven A. Rosenberg, Thomas A. Waldmann, Nicholas P. Restifo

Research output: Contribution to journalArticlepeer-review

Abstract

IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+ memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+ T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+ T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+ T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8 + T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.

Original languageEnglish (US)
Pages (from-to)1969-1974
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number7
DOIs
StatePublished - Feb 17 2004

ASJC Scopus subject areas

  • General

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